Response to immune complex vaccine in chronic hepatitis B patients is associated with lower baseline level of serum IgG galactosylation

Abstract

The composition of glycan in immunoglobulin G (IgG) has shown to affect various diseases and can be regulated by drugs and preventive vaccination. A hepatitis B surface antigen (HBsAg)-hepatitis B immunoglobulin (HBIG) immune complex (YIC) therapeutic vaccine for chronic hepatitis B (CHB) patients has undergone clinical trials. To explore for markers of CHB, which could be associated with responsiveness to YIC therapeutic vaccine, serum IgG glycosylation in CHB patients was analyzed. Kinetic changes of serum galactosylated IgG in 53 hepatitis Be antigen (HBeAg)-positive CHB patients treated with YIC were monitored by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) analysis. Whole blood cytokines were assayed by cytokine binding assay kits. All samples were back assayed before treatment, during therapy and follow-up for 6 months from a previous completed clinical trial. During YIC treatment, 26 patients with lower IgG galactosylation level at baseline [galactosylation level (Gal-ratio) = -0.29, 0.18 (mean, SD)] showed sustained increase of serum galactosylated IgG, and responded to YIC treatment by HBeAg seroconversion. While those who did not respond to YIC treatment [Gal-ratio = -0.40, 0.15 (mean, SD)] failed to show similar changes. Furthermore, this kinetic increase of galactosylated IgG correlated with marked up-regulated IL-2 level, confirming that effective cellular immune responses have participated in responsiveness. For HBeAg-positive CHB patients lower serum IgG galactosylation level may serve as an indicator for selecting a suitable subpopulation of candidates for YIC therapeutic vaccination. Abbreviations: ADCC = antibody-dependent cell-mediated cytotoxicity, ALT = alanine aminotransferase, AUC = area under the curve, CHB = chronic hepatitis B, Fc = fragment crystallizable, G0 = fucosylated biantennary glycan carrying no galactose, G1 = fucosylated biantennary glycan carrying one galactose, G2 = fucosylated biantennary glycan carrying two galactose, Gal-ratio = galactosylation level, GEEs = generalized estimating equations, HBeAg = hepatitis Be antigen, HBIG = hepatitis B immunoglobulin, HBsAg = hepatitis B surface antigen, HBV = hepatitis B virus, IgG = immunoglobulin G, MALDI = matrix-assisted laser desorption/ ionization, MS = mass spectrometry, QIT = quadrupole ion trap, ROC = receiver operator characteristic, TOF = time of flight, YIC = hepatitis B surface antigen-hepatitis B immunoglobulin immune complex. Keywords: chronic hepatitis B, galactosylation, hepatitis Be antigen seroconversion, immunoglobulin G, therapeutic vaccine